rabies, world rabies day
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Rabies, World Rabies DayTRANSCRIPT
Rabies Rhabdovirus
basics
Dr.T.V.Rao MD
Dr.T.V.Rao MD 1
Early Rabies
• Rabies has been recognized in
India since the Vedic period (1500–
500 BC) and is described in the
ancient Indian scripture Atharvaveda,
• Rabies is endemic in India, a vast
country with a population exceeding
1.2 billion and a land area of 3.2
million km. Dr.T.V.Rao MD 2
Dr.T.V.Rao MD 3
Rabies widely spread in Asia and
Africa
• Rabies is widely distributed across
the globe. More than 55 000 people
die of rabies each year. About 95% of
human deaths occur in Asia and
Africa.
• Most human deaths follow a bite from
an infected dog. Between 30% to
60% of the victims of dog bites are
children under the age of 15. Dr.T.V.Rao MD 4
What is Rabies
• Rabies is a Zoonotic viral disease Rabies
infects domestic and wild animals, and is
spread to people through close contact
with infected saliva (via bites or
scratches). The disease is present on
nearly every continent of the world but
most human deaths occur in Asia and
Africa (more than 95%). Once symptoms
of the disease develop, rabies is fatal.
Dr.T.V.Rao MD 5
Rabies - Common facts
• Mad Dog biting Humans lead to Rabies.
• Latin word Rabhas means Frenzy.
• Hydrophobia Fear of Water, Saliva of
Rabid dogs
• Pasture’s success – Vaccination
Fixed virus from Rabbit injected into
Joseph Meister
Injected 13 injection of the cord vaccine.
Dr.T.V.Rao MD 6
7
Rabies- A Zoonotic Disease • Rhabdovirus family;
genus Lyssavirus
• Enveloped, bullet-shaped virions
• Slow, progressive zoonotic disease
• Primary reservoirs are wild mammals; it can be spread by both wild and domestic mammals by bites, scratches, and inhalation of droplets.
Dr.T.V.Rao MD 7
Rabies – A fatal Zoonotic
Disease
Dr.T.V.Rao MD 8
Rabies in USA
• Most of the recent
human rabies cases
in the United States
have been caused by
rabies virus from
bats. Awareness of
the facts about bats
and rabies can help
people protect
themselves, their
families, and their
pets. Dr.T.V.Rao MD 9
Rhabdovirus
• A Bullet shaped virus/
Enveloped
• Contains ss RNA
virus
• Rhabdoviridae –
infects mammals.
• Important virus
Lyssa virus- Rabies
virus
Lyssa means
Rage. Dr.T.V.Rao MD 10
Rabies virus • Bullet shaped virus
• Size is 180 x 75 nm
• Has Lipoprotein
envelop
• Knob like spikes
/Glycoprotein S
• Genome un
segmented
• Linear negative sense
RNA Dr.T.V.Rao MD 11
What is a Fixed Virus
• One whose virulence and incubation period have been stabilized by serial passage and remained fixed during further transmission.
• Rabies virus that has undergone serial passage through rabbits, thus stabilizing its virulence and incubation period and called as fixed virus
Dr.T.V.Rao MD 12
What is a Street Virus
• Virus from a naturally infected animal, as opposed to a laboratory-adapted strain of the virus.
• The virulent rabies virus from a rabid domestic animal that has contracted the disease from a bite or scratch of another animal, and
called as street virus.
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Any mammal can get rabies.
Raccoons, skunks, foxes and bats
• Dogs, cats, cattle and ferrets
• Humans too
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What kind of animals
get Rabies?
• The rabies virus can infect all
mammals.
• Mammals are warm-blooded
animals that have hair and
mammary glands to produce
milk for their babies.
• Animals like frogs, birds, and
snakes do not get rabies.
Dr.T.V.Rao MD 15
Man’s best friend
but can spread Rabies if not vaccinated
Dr.T.V.Rao MD 16
Rabies viruses are sensitive to
common Chemicals
• The virus is sensitive to
Ethanol
Iodine
Soap / Detergents
Ether, Chloroform, Acetone
Destroyed at 500 c in 1 hour
at 600 c in 5 minutes.
Dr.T.V.Rao MD 17
Antigenic properties
• Surface spikes
composed of
Glycoprotein G
• Produces
Pathogenicity by
binding to Acetyl
choline receptors in
the neural tissue
• Stimulate T
lymphocytes
Cytotoxic effect. Dr.T.V.Rao MD 18
Transmission
• Abrasions or scratches on skin.
• Mucous membrane exposed to saliva.
• Most frequently via deep penetrating bite wounds.
• Other routes.
Inhalation in bat infected caves.
Ingestion of dead /infected animal meat
Corneal transplantation
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Dr.T.V.Rao MD 20
Pathogenesis of Rabies
• Bite by Rabid dog or other animals
• Virus are carried in saliva virus deposited on the wound site.
• If untreated 50% will Develop rabies.
• Rabies can be produced by licks and corneal transplantation.
• Virus multiply in the muscle ,connective tissue, nerves after 48 – 72 hours.
• Penetrated nerve endings. Dr.T.V.Rao MD 21
PATHOGENESIS
Live virus Epidermis, Mucus membrane
Peripheral nerve
CNS ( gray matter )
Other tissue (salivary glands,…)
centripetally
centrifugally
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Spread of Virus
• From Brain virus
spread to
Salivary glands,
Conjunctival cell
released into tears
Kidney
Lactating glands
and Milk after
pregnancy
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Pathogenesis
• Virus travels through axoplasam toward
the spinal cord, at the rate of 3 mm/hour,
• Towards the brain
• Spread from brain centrifugally to various
parts of the body.
• Multiplies in the salivary glands and shed
in the saliva.
• Cornea, facial tissues skin.
Dr.T.V.Rao MD 28
Pathogenesis
• Incubation 1 – 3 months.
• May be average from 7 days to 3
years.
• Stages of the disease.
Prodrome
Acute encephalitis.
Coma / Death. Dr.T.V.Rao MD 29
Broad category - Presentations
• Furious Rabies
• Dumb ( Rage
tranquille )
•
(Landry/Guillain
-Barre
Syndrome Dr.T.V.Rao MD 30
Category - WHO
• Category I: touching or feeding suspect
animals, but skin is intact
• Category II: minor scratches without
bleeding from contact, or licks on broken
skin
• Category III: one or more bites, scratches,
licks on broken skin, or other contact that
breaks the skin; or exposure to bats
Dr.T.V.Rao MD 31
Clinical Findings
• Bizarre behavior.
• Agitation
• Seizures.
• Difficulty in drinking.
• Patients will be able to eat solids
• Afraid of water - Hydrophobia.
• Even sight or sound of water disturbs the patient.
• But suffer with intense thirst.
• Spasms of Pharynx produces choking
• Death in 1 -6 days.
• Respiratory arrest / Death / Some may survive.
Dr.T.V.Rao MD 32
• Headache, fever, sore throat
• Nervousness, confusion
• Pain or tingling at the site of the bite
• Hallucinations
– Seeing things that are not really there
• Hydrophobia
– “Fear of water" due to spasms in the throat
• Paralysis
– Unable to move parts of the body
• Coma and death
Symptoms
Dr.T.V.Rao MD 33
CLINICAL MANIFESTATIONS
1 – Non specific prodrome
2 – Acute neurologic encephalitis Acute encephalitis Profound dysfunction of brainstem
3 – Coma
4 - Death ( Rare cases recovery ) Dr.T.V.Rao MD 34
CLINICAL MANIFESTATIONS
Non specific prodrome
1 - 2 days 1 week
Fever, headache, sore throat
Anorexia, nausea, vomiting,
Agitation, depression
Parenthesis or fasciculation's at
or Around the site of inoculation of
virus.
Dr.T.V.Rao MD 35
Acute Neurologic Encephalitis
• 1– 2 days to < 1 week
• Excessive motor activity, Excitation, Agitation
• Confusion, Hallucinations, Delirium,
• Bizarre aberrations of thought, Seizures,
• Muscle spasms, Meningismus,
• Opisthotonic posturing
• Mental aberration ( Lucid period coma )
• Hypersalivation, Aphasia, Pharyngeal spasms
• Incoordination, Hyperactivity
Dr.T.V.Rao MD 36
Acute Neurologic Encephalitis
Phase - Presentations
• Fever T > 40.6
• Dilated irregular pupils
• Lacrimation, Salivation & Perspiration
• Upper motor neuron paralysis
• Deep tendon reflexes
• Extensor plantar responses ( as a rule )
• Hydrophobia or Aerophobia (50 -70% )
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Rabies can present as Grave
condition
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Majority will succumb to Disease
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Clinical presentation –clues in
Diagnosis Leads
• In most cases, human rabies is diagnosed primarily on the basis of clinical symptoms and signs, and a corroborative history of or evidence of an animal bite, death of an animal, and incomplete or no vaccination following exposure. The facility for laboratory diagnosis and confirmation of rabies, be it in humans or in animals, is available premortem in only a few institutions in India can diagnose.
Dr.T.V.Rao MD 40
Laboratory Diagnosis
• Survival possible? May need Laboratory Diagnosis
• Clinical differentiation other cases of Encephalitis.
• Post mortem Diagnosis by
By demonstration of Negri bodies.
Isolation of virus fro Mice brain
inoculation.
tissue culture on culture lines
W 138, BHK,
PCR emerging method.
IF methods corneal impression method.
Dr.T.V.Rao MD 41
Common confirmatory test -
Rabies 1. The standard
premortem test
is a fluorescent
antibody test to
demonstrate the
presence of viral
antigen. The standard
post-mortem test is
biopsy of the patient's
brain and examination
for Negri bodies. Autopsies are rarely performed.
Dr.T.V.Rao MD 42
DIAGNOSIS
•Laboratory finding: ( CBC, CSF )
•Exclusion of other etiologies
•Pathology: Formation of cytoplasmic inclusions:
( Negri bodies )
( Ammon’s horn, Cerebral cortex,
Brainstem, Hypothalamus,
The Purkinje cells of cerebellum,
Dorsal spinal ganglia ) Dr.T.V.Rao MD 43
Diagnostic methods
• Antigen detection by specific Immuno fluorescence.
Ante-mortem - Conjunctival,skin biopsy from nape of neck.
Postmortem impression from surfaces of salivary glands Hippocampus,
Histological examination
ELISA specific antibody detection.
PCR
Dr.T.V.Rao MD 44
Negri bodies – A gold
standard in Diagnosis • Inclusion
bodies called
Negri bodies
are 100%
diagnostic for
rabies infection,
but found only
in 20% of cases Dr.T.V.Rao MD 45
Negri bodies
in Brain Tissue
• Negri bodies round or oval inclusion bodies seen in the cytoplasm and sometimes in the processes of neurons of rabid animals after death.
• Negri bodies are Eosinophilic, sharply outlined, pathognomonic inclusion bodies (2-10 µm in diameter) found in the cytoplasm of certain nerve ..
Dr.T.V.Rao MD 46
Emerging Methods in Diagnosis
• The reference method for diagnosing rabies is by performing PCR or viral culture on brain samples taken after death. The diagnosis can also be reliably made from skin samples taken before death. It is also possible to make the diagnosis from saliva, urine and cerebrospinal fluid samples, but this is not as sensitive. Inclusion bodies called Negri bodies are 100% diagnostic for rabies infection, but found only in 20% of cases.
Dr.T.V.Rao MD 47
DIFFERENTIAL DIAGNOSIS
Other viral encephalitis
Hysteria reaction to animal bite
Landry/Guillan-barre syndrome
Poliomyelitis
Allergic encephalomyelitis ( rabies vaccine )
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PREVENTION
Preexposure Prophylaxis
Post exposure Prophylaxis
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Ist Vaccine for Rabies
• Prepared by Pasteur by drying various periods pieces of spinal cord of Rabbits infected with fixed virus
• 1885 Joseph Meister 9 year boy vaccinated 13 injections were given
• Patient saved
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Preexposure vaccination
• Indicated in
Laboratory
workers
Veterinarians
and technical
staff.
Bat handlers. Dr.T.V.Rao MD 51
Supporting care in
Animal/Dog Bites
Dr.T.V.Rao MD 52
Basic care in Animal bites
• Before exposure to infection
In Veterinary surgeons animal handlers.
Specific Prophylaxis
After exposure to Dog bite.
Local treatment
Cauterization
Scrub with Soap and clean.
Use cetavalon, tincture of Iodine
Antirabic serum don't suture wound unless highly essential.
Dr.T.V.Rao MD 53
• Tell an health care
worker immediately
• Wash the wound
out with soap and
water
• Inform the doctor
right away
If you are bitten or scratched
Dr.T.V.Rao MD 54
POSTEXPOSURE PROPHYLAXIS
1 – Wound cleaning & treatment
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Dr.T.V.Rao MD 57
Post exposure vaccination
• Anti Rabies vaccines are given when
person is
1 Bitten
2 Scratched
3 Licked
By Rabid animal
animal to be kept for 10 days ?
Dr.T.V.Rao MD 58
Category - WHO
• Category I: touching or feeding suspect
animals, but skin is intact
• Category II: minor scratches without
bleeding from contact, or licks on broken
skin
• Category III: one or more bites, scratches,
licks on broken skin, or other contact that
breaks the skin; or exposure to bats
Dr.T.V.Rao MD 59
Vaccines • Semple vaccine Contain 5 % suspension. Of infected
Sheep brain, ( Infected with fixed virus )
Inactivated with Phenol at 370c
Vaccines available after inactivation with Beta propiolactone Used in India
Vaccine contains Nucleic capsid antigen,
Small quantities of Glycoprotein G
Used in Developed countries Neural complications.
Dr.T.V.Rao MD 60
*Dose Semple Vaccine
Semple vaccine BPL vaccine
Class I 2ml x 7 days 2mlx7 days
Class II 5ml x 14 days 5mlx10days
Class III 10ml x 14 days 5 ml x 10 days
* Many health institues abandoded its use
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Neural Vaccines*
• Class I slight risk
• Class II Moderate risk
• Class III Great risk
• Neural vaccines may cause Neuroparlytic
complications, Laundry’s type ascending
paralysis • Dose is regulated according to grade/class of bites
• Many countries do not use in view of neurological
complications
Dr.T.V.Rao MD 62
HUMAN RABIES Cell culture
Vaccines Vaccine: Human diploid cell vaccine (HDCV)
Developed by Koprowsky,Wiktor,and
Plotkin
Purified chick embryo cell vaccine
(PCEC)
Purified Vero cell vaccine (PVRV)
Purified duck embryo vaccine (PDEV)
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Post exposure Prophylaxis WHO
• Category Type of exposure prophylaxis
1 Touching and feeding No
2 licking on intact skin Minor scratches, licks Start vaccine
on broken skin
3 Transdermal bites contaminated Rabies Immunoglobin
+ Vaccine
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Post exposure Prophylaxis
• The vaccination is given on
0, 3, 7, 14, 30, and 90th day
Immunity lasts for 5 years
Injected on deltoid region IM/SC
Not to be given in the gluteal region
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POSTEXPOSURE PROPHYLAXIS
3 – Active immunization
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Cell culture Vaccines
Commonly prescribed
1 Human diploid
cell vaccine.
2 Purified chick
embryo cell
vaccine
3.Purified Vero
cell vaccine
Dr.T.V.Rao MD 67
Human Diploid Cell
Vaccine
• Koprowsky, Viktor,
Plokin discovered
• Inactivated in
Betaproprionate.
• No serious side
effects.
• Human Diploid cell
vaccines purified .
• Sub Unit vaccines in
progress/developed. Dr.T.V.Rao MD 68
Human Diploid Cell Vaccines
• Dosage • Preexposure prophylaxis
0 – 7 – 21 – or 28 – 56 days
A booster after 1 year,
Repeat once in 5 days,
Post exposure Prophylaxis Six doses
0 -3 -7-14 – 30 - 90 days
Given IM or SC in the Deltoid region
Don't inject inGluteal region.
Dr.T.V.Rao MD 69
Preexposure prophylaxis doses
• Given on the
following days
0, 7, 21,or 28
and 56th day
Generally given
to Vetnary
personal
Dr.T.V.Rao MD 70
Passive Immunization
• Human Rabies
Immunoglobulin HRIG
• High Risk bitten on
face and neck
• Given a dose of 20 IU
/Kg wt.
• Half at the site of bite
and rest IM route.
• Active immunization
should be initiated with
passive immunization. Dr.T.V.Rao MD 71
Future of Rabies Vaccines
• A number of experimental vaccines are under development that may provide alternative safe and potent but less expensive vaccine options. These include DNA vaccines, recombinant viral vaccines, and recombinant protein vaccines. Further testing is needed to determine if and which one of these novel vaccines will make their way into mass production and application in the future.
Dr.T.V.Rao MD 72
Subunit or Genetically
Engineered vaccines for Rabies
• A viral immunizing agent
that has been treated to
remove traces of viral
nucleic acid so that only
protein subunits remain.
The subunits have less
risk of causing adverse
reactions.
• Several trails in
progress
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Epidemiology
• No Danger of Nursing Rabies patients but do take precautions
• Any animal bite can cause Rabies except Mice
• BATS in caves in spread he disease by respiratory disease.
• India around 30,000 die with Rabies.
• Vaccination of the Dogs and Licensing of the Dogs Dr.T.V.Rao MD 74
In spite of Health Education several die due
to Rabies infection in Developing world
Dr.T.V.Rao MD 75
World's Rabies Day (on September 28)
• World Rabies Day
is a cooperative
global event
planned to reduce
the suffering from
rabies. This day
celebrates Dr.
Louis Pasteur’s
vision of a rabies
free world. Dr.T.V.Rao MD 76
Never touch an unfamiliar or wild
animal.
Always ask permission to touch
someone else’s pet.
Dr.T.V.Rao MD 77
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